Uremic Toxin Indoxyl Sulfate and Progression of Chronic Kidney Disease

Chronic kidney disease is a progressive disease, which is characterized by a decline in renal function due to various underlying causes. A frequent outcome shared by nearly all chronic and progressive nephropathies is renal fibrosis. Current evidence highlights multiple mechanisms involved in renal fibrosis, including natural aging processes, glomerular hyperperfusion, intratubular hypertension and hyperfiltration, alterations in the expression of mediators responsible for cellular and structural damage, etc. The progression of fibrosis is accompanied by the decline in the renal function, resulting in uremic syndrome characterized by the accumulation of various substances known as uremic toxins. They include low-molecular water-soluble compounds, protein-bound molecules, and medium-molecular compounds. Recent studies suggest that uremic toxins can contribute to the progression of fibrosis. This review summarizes data from retrospective, prospective, and experimental studies, and systematic reviews regarding the impact of uremic toxins on the progression of renal fibrosis. The data were retrieved from bibliographic databases such as MedLine, PubMed, Google Scholar, Scopus, and eLibrary. Only articles published in peer-reviewed scientific journals were included. The search strategy was based on the key terms including хроническая болезнь почек (chronic kidney disease), уремические токсины (uremic toxins), индоксил сульфат (indoxyl sulfate), фиброз почек (renal fibrosis), and эпителиально-мезенхимальный переход (epithelial-mesenchymal transition). Lists of all relevant articles and systematic reviews were manually examined. A total of 114 full-text articles were reviewed, with 60 selected for this review. The review highlights the role of indoxyl sulfate as an active contributor to renal fibrosis, rather than a consequence of chronic kidney disease.